Method for Screening for Compounds Safe for Gastric Mucosa

Abstract

A method for screening for compounds or salts thereof, in particular nonsteroidal anti-inflammatory compounds or salts thereof, that are safe for gastric mucosa and cause little gastrointestinal side effects. The method uses a particular liposome to serve as a cell membrane model. The liposome encapsulates a fluorescent dye, in particular, calcein and is formed of phospholipids, such as phosphatidylcholine, phosphatidylglycerol, phosphatidylserine, and phosphatidylinositol. A test compound is allowed to react with the liposome and the leakage of the fluorescent dye from the liposome is evaluated. As a result, compounds safe for gastric mucosa, in particular, anti-inflammatory compounds can be screened.

1 . A method for screening for compounds safe for gastric mucosa, comprising:
 preparing liposomes, serving as a cell membrane model, that are formed of a phospholipid and encapsulate a fluorescent dye;   allowing a test compound to react with the liposomes; and   evaluating the leakage of the fluorescent dye from the liposomes.   
     
     
         2 . The method for screening according to  claim 1 , wherein the phospholipid for use in the cell membrane model is selected from the group consisting of phosphatidylcholine, phosphatidylglycerol, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, and cardiolipin. 
     
     
         3 . The method for screening according to  claim 1 , wherein evaluation of the leakage of the fluorescent dye comprises measuring fluorescence emitted from the dye at an excited wavelength. 
     
     
         4 . The method for screening according to  claim 1 , wherein the fluorescent dye is selected from the group consisting of calcein, rhodamine, and fluorescein derivatives. 
     
     
         5 . The method for screening according to  claim 4 , wherein the fluorescent dye is calcein. 
     
     
         6 . The method for screening according to  claim 5 , wherein the calcein leakage is determined by measuring fluorescence at 520 nm. 
     
     
         7 . The method for screening according to  claim 1 , wherein the test compound is an anti-inflammatory compound. 
     
     
         8 . The method for screening according to  claim 7 , wherein the anti-inflammatory compound is a nonsteroidal anti-inflammatory compound or a steroid compound. 
     
     
         9 . The method for screening according to  claim 1 , wherein the test compound is a compound that acts to protect gastric mucosa. 
     
     
         10 . An anti-inflammatory compound safe for gastric mucosa, obtained by the method for screening according to  claim 7 , or a salt thereof. 
     
     
         11 . A gastric mucosa-protecting material, obtained by the method for screening according to  claim 9 . 
     
     
         12 . A liposome serving as a cell membrane model for use in the screening of compounds having membrane toxicity to gastric mucosa, the liposome being formed of a phospholipid and encapsulating a fluorescent dye. 
     
     
         13 . The liposome according to  claim 12 , wherein the fluorescent dye is selected from the group consisting of calcein, rhodamine, and fluorescein derivatives. 
     
     
         14 . The liposome according to  claim 12 , wherein the phospholipid for use in the cell membrane model is selected from the group consisting of phosphatidylcholine, phosphatidylglycerol, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, and cardiolipin.